Sayin U, Atasoy S, Uzbay I T, Aricioğlu-Kartal F, Koyuncuoğlu H
DETAM (Experimental and Medical Research Center), Istanbul Faculty of Medicine, Capa, Turkey.
Pharmacol Res. 1998 Jul;38(1):45-51. doi: 10.1006/phrs.1998.0329.
Effects of gamma-vinyl-GABA (GVG), an antiepileptic drug that inhibits GABA transaminase and increases extracellular GABA concentrations in the brain, were investigated on the morphine abstinence syndrome (AS) in male Wistar rats. Two morphine pellets (75 mg morphine base in each) were implanted subcutaneously on the back of the rats. Seventy-two hours after the morphine implantation, naloxone (NL, 2 mg kg-1) was injected intraperitoneally (i.p.) to induce precipitated morphine AS. GVG was administered at the doses of 250 mg kg-1 (n = 11) and 500 mg kg-1 (n = 11) i.p. 24 h prior to AS and at the dose of 500 mg kg-1 (n = 13) i.p. 6 h prior to AS. Immediately after NL injections, rats were observed for 5 min and AS signs (jumping, teeth chattering, wet dog shake, diarrhoea, ptosis and defecation) were assessed. The behavioural signs of GVG-treated rats were compared with the control groups (n = 10) during the AS. Jumping, wet dog shake, teeth chattering were found to be significantly increased in all of the GVG-treated groups. Ptosis was found to have increased in only 500 mg kg-1 GVG groups. GVG potentiated the severity of morphine AS signs. GVG does not seem to have any therapeutic potential for treatment of morphine abstinence unlike some other drugs that enhance GABAergic transmission.
研究了抗癫痫药物γ-乙烯基-GABA（GVG）对雄性Wistar大鼠吗啡戒断综合征（AS）的影响，该药物可抑制GABA转氨酶并增加大脑细胞外GABA浓度。在大鼠背部皮下植入两颗吗啡丸（每颗含75 mg吗啡碱）。吗啡植入72小时后，腹腔注射纳洛酮（NL，2 mg kg-1）以诱发急性吗啡AS。在AS前24小时，GVG以250 mg kg-1（n = 11）和500 mg kg-1（n = 11）的剂量腹腔注射，在AS前6小时，GVG以500 mg kg-1（n = 13）的剂量腹腔注射。注射NL后立即观察大鼠5分钟，并评估AS体征（跳跃、牙齿打颤、湿狗样抖动、腹泻、眼睑下垂和排便）。在AS期间，将GVG处理组大鼠的行为体征与对照组（n = 10）进行比较。发现在所有GVG处理组中，跳跃、湿狗样抖动、牙齿打颤均显著增加。仅在500 mg kg-1 GVG组中发现眼睑下垂有所增加。GVG增强了吗啡AS体征的严重程度。与其他一些增强GABA能传递的药物不同，GVG似乎对治疗吗啡戒断没有任何治疗潜力。
